Event Details This webinar will introduce the Advanced MethylDetox Profile, discuss the scientific underpinnings of methylation and detoxifications, and explain how this test can benefit your patients. Our speakers have a diverse range of backgrounds from research to clinical practice. Key Learning Points -Discover the critical genes in the methylation pathway -Understand each gene’s role in patient methylation function -See how the MethylDetox Profile can be used clinically -Learn how to monitor treatment progress

1. .Exploring the MethylDetox Profile

2. will begin momentarily
Exploring the MethylDetox Profile

3. As Always…
Tonight’s discussion does not take into consideration
your patient’s medical history, drug/supplement
interactions and/or allergies/sensitivities. It is the
responsibility of the practitioner to determine
appropriate supplement and dosing choices for each
patient.

4. About the Speakers
• Friedrich Schiller Universitaet – Heidelberg, Germany
• Institut National de La Recherche Agronomique - France
• Krankenhaus Harlaching -Germany
Dr. Dino Celeda holds a Ph.D in Biology specialized in
Human Genetics from the Ruprecht Karls Universitaet,
Heidelberg, Germany. He completed his training and held
positions at many renowned institutions including:
Dr. Celeda has authored numerous publications in the field of Human Genetics. Included in
his experience are Senior R&D, Scientific Advisor, Director of Genetic Testing and Director of
Science positions.
Dr. rer. nat. Dino Celeda (PhD)
Scientific Officer

5. About the Speakers
Roger Davis Deutsch is one of the
pioneers of food and chemical
sensitivities testing with involvement
in this field since 1986. He has been
responsible for the
commercialization of the Alcat Test
throughout the world. He is the co-
author of Your Hidden Food Allergies
are Making You Fat. Roger serves as
the Founder and CEO of Cell Science
Systems.

6. About the Speakers
Jim Hoover has been with
Cell Science Systems for six
years and currently serves
as the Sales Director for the
company.

7. Objectives
Identify themostimportant genesinvolved inthemethionine/
homocysteine cycle:
• mutations (SNPs), controlling methionine/homocysteine cycle.
• impact on homocysteine levels.
Personalized intervention according tothegenetic testresult:
• Targeted nutrition
• Targeted supplementation
• Monitoring of individual progress by measuring homocysteine
levels in the blood

8. Homocysteine, Glutathione,
Mitochondria & Metals
Methionine
COMT
CBS
CSE
B6
CDO
Cysteine sulfinate
SO4
2-, Taurine
SO4
2-
SOD2
O2-
H2O2
AHCY
Methylation-
potential
(SAMe/SAH ratio)
SAMe
SAH
Homocysteine
Methylcobalamine
GSSG
H2O
H2O2
GPX1
Glutathione
CBS
B6
Cystathionine
CSE
Cysteine
H2S
B6
GCLC
GCLM
GSTM1
Folic acid
THF
MTR
MTRR
5-Methyl THF
5,10-Methylene THF
MTHFR
1. Methylation:
-DNA
-Neurotransmitters
-Drugs
-Toxins
2. Glutathione- synthesis
Phase II detoxification
3. Mitochondria
Oxidative Stress protection in
ATP prod.
4. Detoxification
by
Glutathione-S-Conjugation

9. Genetic Polymorphism (SNP)
Genetic Polymorphism (SNP):
Genome News Network . J. Craig Venter Institute 2000 - 2004

10. Genetic Polymorphism (SNP)
A SNP can lead to a change in protein sequence and thus influence the 3-D
conformation. In the example here, the SNP disrupts hemoglobin formation and
causes sickle cell anemia.

11. Functional Genetic Test Results
The individual’s functional genetic test results are shown on a level
of functionality and/or expression of the corresponding enzyme.
• homozygous positive, -;-, both alleles from both parents
show mutation. Reduced function/expression.
• heterozygous +;-, one allele from one parent shows
mutation, the other allele shows the normal, wild-type. 50%
of the genes are normal
• homozygous negative +;+, both alleles from both parents
have no mutation and show the normal, wild type. 100% of
the genes are normal.

12. Genomic Insights TM
– TEST
Individual’s current status: testing of relevant SNPs and
corresponding metabolic markers in blood
– TARGET
Targeted intervention: personalized, specific supplementation
according to individual results of relevant of SNPs, and
corresponding metabolic markers in blood
– MONITOR
Individual progress: monitoring and maintaining the progress
of personalized, specific supplementation with measurement
of metabolic markers in blood
Applying Functional Genetics for targeted intervention
by personalized, specific supplementation

13. Genes in the Methionine/Homocysteine
Cycle
• MTHFR (Methylenetetrahydrofolate reductase)
C677T and A1298C mutations in the MTHFR gene are known to cause a diminished methylation
capacity, by a reduction in 5-MTHF synthesis.
• Methionine synthase (MS)
MS is encoded by the 5-methyltetrahydrofolate-homocysteine-methyltransferase gene (MTR). Its task
is to generate methionine from homocysteine by using methylcobalamin (methylated vitamin B12)
obtained when 5-MTHF donates its methyl group to vitamin B12. The mutation at position C3518T in
the gene is described with a reduced activity of the resulting enzyme.
• MTRR(5-Methyltetrahydrofolate-Homocysteine
Methyl-Transferase Reductase)
codes for the enzyme methionine synthase reductase. The methionine synthase reductase
enzyme is responsible to keep Methionine synthase (MS see above) in an active (reduced)
form in order to guarantee the proper conversion of homocysteine to methionine. Both
enzymes function together in a so called “ping-pong reaction. If the process is inefficient
because of a mutation, in both genes, homocysteine builds up and the methylation is impaired..

14. • COMT (Catechol-O-Methyltransferase)
COMT is responsible for the transfer of the methyl group from SAMe to specific substances (e.g.
catecholamines) for removal. COMT is also involved in drug metabolism/clearance, neurotransmitter
regulation, gene expression as well as in the detoxification of a variety of environmental toxins.
The mutations at position G472A (Val108/158Met) and G304A (Ala52/102Thr) are described with a
reduced activity of the resulting enzyme.
• AHCY (S-Adenosylhomocysteine hydrolase)
SAMe is converted to S-Adenosylhomocysteine (AdoHcy) after the donation of its methylgroup by
COMT. High levels of AdoHcy, however impair the methylation by SAMe and reduce the
“methylation potential” of the body. In order to maintain proper methylation potential ADoHcy,
must be converted again to homocysteine by the enzyme AHCY. It is crucial that AdoHcy is converted
immediately by AHCY to homocysteine and adenine because it has a higher affinity to COMT and
thus can even block methylation processes.
Genes in the Methionine/Homocysteine
Cycle

15. Treatment Monitoring
• Homocysteine
Measurement of homocysteine levels in serum for monitoring and
maintaining treatment progress.

16. Homocysteine, Glutathione,
Mitochondria & Metals
Methionine
COMT
CBS
CSE
B6
CDO
Cysteine sulfinate
SO4
2-, Taurine
SO4
2-
SOD2
O2-
H2O2
AHCY
Methylation-
potential
(SAMe/SAH ratio)
SAMe
SAH
Homocysteine
Methylcobalamine
GSSG
H2O
H2O2
GPX1
Glutathione
CBS
B6
Cystathionine
CSE
Cysteine
H2S
B6
GCLC
GCLM
GSTM1
Folic acid
THF
MTR
MTRR
5-Methyl THF
5,10-Methylene THF
MTHFR
1. Methylation:
-DNA
-Neurotransmitters
-Drugs
-Toxins
2. Glutathione- synthesis
Phase II detoxification
3. Mitochondria
Oxidative Stress protection in
ATP prod.
4. Detoxification
by
Glutathione-S-Conjugation

17. Homocysteine, Methylation, Methylation Potential
Methionine
COMT
CBS
CSE
B6
CDO
Cysteine sulfinate
SO4
2-, Taurine
SO4
2-
SOD2
O2-
H2O2
AHCY
Methylation-
potential
(SAMe/SAH ratio)
SAMe
SAH
Homocysteine
Methylcobalamine
GSSG
H2O
H2O2
GPX1
Glutathione
CBS
B6
Cystathionine
CSE
Cysteine
H2S
B6
GCLC
GCLM
GSTM1
Folic acid
THF
MTR
MTRR
5-Methyl THF
5,10-Methylene THF
MTHFR
1. Methylation:
-DNA
-Neurotransmitters
-Drugs
-Toxins
2. Glutathione- synthesis
Phase II detoxification
3. Mitochondria
Oxidative Stress protection in
ATP prod.
4. Dtoxification
by
Glutathione-S-Conjugation

18. Homocysteine / Methionine
Homocysteine
Methionine

19. Homocysteine, Methylation, Methylation Potential
Methylation potential
(SAMe/SAH ratio)
SAMe
Methionine
SAH
Homocysteine
1. Methylcobalamine (Methyl-Vit.B12)
Folic acid
THF 5-Methyl-THF
5,10-Methylene THF
1. Methylation:
-DNA
-Neurotransmitters
-Drugs
-Toxins
SAH blocks methylation by SAMe
and reduces methylation potential
Genes:
MTHFR: Methylene tetrahydrofolate reductase
(MTR) MS: Methionine synthase
MTRR (MSR): Methionine synthase reductase
COMT: Catechol-O-methyltransferase
AHCY: Adenosyl homocysteinase
Supplementation and co factors:
Folic acid
5-Methyl THF (5-MTHF)
Methylcobalamin (Methyl-Vit.B12)
SAMe
NADH
Vit. B6
Treatment Monitoring:
Homocysteine
Folic acid
5-MethyleneTHF
Methylcobalamine (Methyl-Vit. B12)
Methionine
Methylation potential
Vit B6
COMT
SNP7-8
B6
1. MTR
2. MTRR
MTHFR
SNP 1-2DHFR
SHMT
AHCY
SNP 9-12
2. Glutathione- synthesis
Phase II detoxification
Mitochondrial protection

20. Genotype
Testing
Treatment
Monitoring
• Homocysteine
• Folic acid
• 5-MethyleneTHF
• Vit. B12
• Methionine
• Methylation
potential
• Vit B6
• Folic acid
• 5-MethylTHF
• Methylcobalamin
• SAMe
• NADH
• Vit. B6
Targeted
Supplements
• MTHFR
C677T; A1298C
• MTR
A2756G; C3518T
• MTRR
A66G (Ile22Met)
• COMT
G472A; G304A
• AHCY
c.-C124A; C112T (Arg38Trp);
G367A (Gly123Arg); C56G

21. Homocysteine, Glutathione,
Mitochondria & Metals.
Methionine
COMT
CBS
CSE
B6
CDO
Cysteine sulfinate
SO4
2-, Taurine
SO4
2-
SOD2
O2-
H2O2
AHCY
Methylation-
potential
(SAMe/SAH ratio)
SAMe
SAH
Homocysteine
Methylcobalamine
GSSG
H2O
H2O2
GPX1
Glutathione
CBS
B6
Cystathionine
CSE
Cysteine
H2S
B6
GCLC
GCLM
GSTM1
Folic acid
THF
MTR
MTRR
5-Methyl THF
5,10-Methylene THF
MTHFR
1. Methylation:
-DNA
-Neurotransmitters
-Drugs
-Toxins
2. Glutathione- synthesis
Phase II detoxification
3. Mitochondria
Oxidative Stress protection in
ATP prod.
4. Detoxification
by
Glutathione-S-Conjugation

22. Advanced
MethylDetox
Profile
Sample Results

23. Advanced
MethylDetox
Profile
Sample Results

24. Advanced
MethylDetox
Profile
Sample Results

25. Advanced MethylDetox Profile
Sample Results

26. Advanced MethylDetox Profile
Sample Results

28. Collection Type
Profiles
One blue top vial and gold top
vial are required for the
profile. Gold top vials must be
spun within one hour of draw.
Genetic Only
Buccal swabs allow for easy
and convenient testing.
Buccal swabs can only be
used for genetic testing.
Homocysteine
Serum gold top vials are required
for homocysteine monitoring.
Gold top vials must be spun
within one hour of blood draw.

29. Ordering Options
Advanced MethylDetox Profile
• MTHFR
• MTR
• MTRR
• COMT
• AHCY
• Homocysteine
Basic MethylDetox Profile
• MTHFR
• MTR
• COMT
• Homocysteine
Advanced MethylDetox Profile
Genetic Only
• MTHFR
• MTR
• MTRR
• COMT
• AHCY
Basic MethylDetox Profile
Genetic Only
• MTHFR
• MTR
• COMT
Individual Genes
• MTHFR
• MTR
• MTRR
• COMT
• AHCY
Homocysteine
• Homocysteine

30. Exploring the
MethylDetox
Profile Q&A

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